POC proposes to develop a new class of submicroscopic chemical sensors for use in the investigation of cellular physiology. These sensors, which can have characteristic dimensions much smaller than l micromole, have the potential for monitoring ionic concentrations, enzyme levels, drug concentrations, and a wide variety of other intracellular chemical properties, with relative ease to the researcher. In the proposed approach, chemically sensitive indicators would be immobilized by photopolymerization at the tip of finely tapered optical fibers similar to those used in Near-field Scanning Optical Microscopy (NSOM). The technique could thus combine the ultrafine resolution of NSOM with the sensitivity and specificity of active fiber optic chemical sensors. The proposed sensors offer significant advantages, including faster response time and minimization of cellular damage, when compared with existing (electrochemical) intracellular sensors. During Phase I of the project, POC will demonstrate the practicality of this technique by fabricating and testing sensors capable of measuring intracellular concentrations of metabolites, ions, or other chemical species of biological interest. Phase II will see expansion into the measurement of other analytes, including biochemical substances such as enzymes and immunochemicals, as well as the development of a portable system capable of serving as the basis for a line of commercial intracellular sensing products.